Plague, or the Black Death, is a zoonotic disease that is spread from mammal to mammal by fleas. This mode of transmission demands that the causative agent of this disease, Yersinia pestis, is able to circumvent the host defense systems of both mammals and insects. Much is known about the interaction of Y. pestis with the mammalian host, however, there is only limited understanding of Y. pestis determinants that allow survival and replication in the insect. In recent years the complete genome sequence of Y. pestis has been determined. This sequence information indicates that Y. pestis contains a cluster of genes with significant homology to insecticidal toxin encoding genes of the insect pathogen Photorhabdus luminescens. The goals of this proposal are to determine if this Y. pestis insecticidal complex increases the virulence of this pathogen, either by resulting in increase colonization of the flea or increased transmission of the bacteria from the flea to a mammal. In addition, initial studies to examine the activity of this complex, and the mechanism of secretion of this complex are proposed. [unreadable] [unreadable] Plague is an epidemic disease of antiquity that continues today with approximately 2,000 cases per year. The causative agent Yersinia pestis is maintained in various rodent species across the world and spread via their respective flea vectors. The goals of this proposal are to examine the role of a newly found toxin complex in Y. pestis flea colonization and/or transmission. [unreadable] [unreadable] [unreadable] [unreadable]